The present invention relates to delivery vehicles having active materials entrapped therein. These delivery vehicles are suspended in water immiscible carriers. The present invention allows two incompatible active substances to be delivered together without cross-reactivity so that they keep their full activity until the delivery vehicle is destroyed or the materials leach from the vehicles.
A number of different delivery vehicles have been developed for entrapment of materials. These delivery vehicles include microcapsules, liposomes, other types of lipid vesicles, cellulosic materials and polymer delivery systems. These vehicles are used primarily to carry aqueous solutions of active materials. U.S. Pat. No. 4,911,928, the disclosure which is incorporated herein by reference, is one of the few patents that concerns the entrapment of material in a water immiscible liquid, not an aqueous solution. This patent discloses the making of paucilamellar lipid vesicles which have an amorphous central cavity that can be filled with a water immiscible material such as an oil. The water immiscible material acts as a carrier for a material which is soluble or suspendable in that oil. The oil is carried in the central cavity, not the external phase.
However, for certain uses, even the lipid vesicles described in the aforementioned patent can leak or break down so that cannot be used. This can be disastrous if the encapsulated materials are incompatible. One attempt to achieve the desired results was using a vesicle incorporating a water immiscible material entrapping a water immiscible active and have another active in an external phase. This type of procedure is described in U.S. Pat. No. 5,019,392, the disclosure which is incorporated herein by reference. However, this method also cannot be used for certain materials. One problem is that for stability reasons, the vesicles often work best if there is an external aqueous phase. Similarly, although blends of lipid vesicles carrying two different materials are known (see, e.g., U.S. Pat. No. 4,247,411), these vesicles have not been used for non-aqueous materials (which fall out side the scope of the '411 patent) and these vesicles are only described as being suspended in an external aqueous solution.
Similarly, most microcapsule work has aqueous solutions both as the entrapped material filling the central cavity and as the external phase. Microcapsules are often made by reacting the monomers forming the polymer at an interface or by cross-linking a material such as an alginic acid derivative with a divalent metal ion. If the alginic acid procedure is used, the cross-linked material is formed into a capsule membrane by reaction with a second polymer. U.S. Pat. No. 4,690,682 describes such a procedure.
In interfacial polymerization, the material to be encapsulated and a hydrophilic monomer is emulsified within a hydrophobic continuous phase and a second monomer is then dissolved in the continuous phase. Polymerization occurs at the boundary between the two phases where the two monomers can interact to form the polymeric material. U.S. Pat. No. 4,251,387 discloses this type of technique. By modifying the conditions of reaction, improved microcapsule membranes can be formed.
Still another entrapment technique is shown in U.S. Pat. No. 3,860,490. In this patent, a microorganism is mixed with acrylate and methacrylate monomers and polymerization is allowed to occur to form a gel lattice about the microorganism. After separation, an additional coating of the polymer may be formed about the entrapped material. In one aspect of this patent, a particulate material is used as a carrier to which the microorganisms are absorbed and then the polymeric coating is formed by a polymerization reaction about the particulate.
While all of the foregoing techniques have substantial uses, in certain instances, particularly where the active material to be entrapped is not soluble or dispersible in aqueous solutions, these techniques may not be appropriate. Further, leaching of the active through pores of the microcapsules or liposomes can be a problem in certain circumstances. In addition, some of these vesicular structures or microcapsules are not stable if a water immiscible carrier is used as the external phase.
Accordingly, an object of the invention is to provide a method of making a delivery vehicle which can be suspended in a water immiscible carrier without leaching of the active.
A further object of the invention is to provide a method of entrapping two incompatible materials while preventing them to cross-react.
Another object of the invention is to provide a delivery system for delivering two incompatible materials in a water immiscible carrier.
These and other objects and features of the invention will be apparent for the following description and the claims.